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Special Feature
June 2000

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Copyright 2000 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.2000

Arch Pediatr Adolesc Med. 2000;154(6):632. doi:
Denouement and Discussion: Costello Syndrome

Figure 1. Coarse facial features suggestive of a storage disease are apparent.

Figure 2. The skin over the upper arm appears loose.

Figure 3. Deep creases are present in both the palmar and plantar surfaces.

In 1971 and again in 1977, Costello described a syndrome with characteristic cutaneous findings, dysmorphic features, and multisystem involvement.1 Prenatal polyhydramnios occurs in almost half of affected pregnancies, probably the result of poor fetal swallowing.1 Although almost all affected infants have birth weights greater than the 50th percentile, all manifest feeding difficulties and poor growth after birth.


The facial features are coarse, suggesting a storage disorder. The nasal bridge is flat; the lips, thick; the mouth and tongue, large; and the ears, low set. Epicanthal folds and down-slanting palpebral fissures are present in most infants. Characteristic cutaneous findings include sparse, curly hair, loose skin, hyperpigmentation, and deep creases of the palms and soles. Later in life, many children with this syndrome develop papillomata around the nares, mouth, or anus. Acanthosis nigricans may appear on the neck and axillae. Musculoskeletal findings in most infants include a short neck, increased anteroposterior diameter of the chest, hyperextensible fingers, wide phalanges, abnormal position of the feet, and tight Achilles tendons.1

Cardiovascular problems are common in children with this syndrome. Congenital heart defects include atrial or ventricular septal defects, pulmonary stenosis, bicuspid aortic valve, patent ductus arteriosus, and mitral valve prolapse.2 Hypertrophic cardiomyopathy and dysrhythmias have been described in more than half of the reported cases but have resulted in minor problems in most patients.1

All patients described with this syndrome have had severe mental and developmental delay; however, an outgoing personality has been described in more than 90% of 37 patients reported.1 Less commonly reported features include hepatosplenomegaly, cataracts, heat intolerance, increased sweating, and graying hair. Abnormal laboratory findings have included delayed bone age, osteoporosis, fasting hypoglycemia, and postprandial hyperglycemia.1


Patients with this syndrome have been considered to have other disorders, including cutis laxa, Noonan syndrome, Donahue syndrome (leprechaunism), Williams syndrome, and lipodystrophy. Careful attention to the constellation of findings, particularly the unusual skin findings in Costello syndrome, should help in differentiation.


The cause of Costello syndrome has not been determined. Most cases reported have been sporadic, although siblings have been described on 2 occasions.1 An association with advanced parental age has been noted, which has been described in conditions with germline mutations.1 A single case with a chromosomal translocation of 1q and 22q may provide clues to localization of a genetic defect.3 In addition, defects of elastic fibers, possibly relating to alternative splicing in the elastin gene or to defects in elastin microfibrils, has been observed in patients with this syndrome.4 The varied manifestations, particularly physical features suggestive of a storage disease, the growth disturbances, hypertrophic cardiomyopathy, and occasional hepatosplenomegaly, suggest a metabolic disorder.

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Article Information

Accepted for publication October 22, 1999.

Reprints: Jia-Woei Hou, MD, Department of Pediatrics, Chang Gung Children's Hospital, 5 Fu-Shing St, Kwei-Shan, Troyuan, Taiwan.

Johnson  JPGolabi  MNorton  ME  et al.  Costello syndrome: phenotype, natural history, differential diagnosis, and possible causes. J Pediatr. 1998;133441- 448Article
Siwik  ESZahka  KGWiesner  GLLimwongse  C Cardiac disease in Costello syndrome. Pediatrics. 1998;101706- 709Article
Czeizel  AETimar  L Hungarian case with Costello syndrome and translocation t(1,22). Am J Med Genet. 1995;57501- 503Article
Mori  MYamagata  TMori  Y  et al.  Elastic fiber degeneration in Costello syndrome. Am J Med Genet. 1996;61304- 309Article